Description:
The main purpose of the study is to define maximum tolerated dose (MTD), recommended Phase II
dose (RP2D) of Peposertib in combination with capecitabine and radiotherapy (RT) in Phase Ib
and to evaluate the efficacy of Peposertib in terms of Pathological Clinical Response
(pCR)/Clinical Complete Response (cCR) when administered in combination with capecitabine and
RT versus placebo, capecitabine, and RT in Phase II.
Title
- Brief Title: Study of Peposertib in Combination With Capecitabine and RT in Rectal Cancer
- Official Title: A Multicenter Study With an Open-label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor Peposertib (M3814) in Combination With Capecitabine and RT in Participants With Locally Advanced Rectal Cancer
Clinical Trial IDs
- ORG STUDY ID:
MS100036_0020
- SECONDARY ID:
2018-002275-18
- NCT ID:
NCT03770689
Conditions
- Locally Advanced Rectal Cancer
Interventions
Drug | Synonyms | Arms |
---|
Phase Ib: Peposertib | M3814, MSC2490484A | Phase Ib: Peposertib + Capecitabine + RT |
Capecitabine | | Phase II: Peposertib + capecitabine + RT |
Phase II: Peposertib | M3814, MSC2490484A | Phase II: Peposertib + capecitabine + RT |
Phase II: Placebo | | Phase II: Placebo + capecitabine + RT |
Purpose
The main purpose of the study is to define maximum tolerated dose (MTD), recommended Phase II
dose (RP2D) of Peposertib in combination with capecitabine and radiotherapy (RT) in Phase Ib
and to evaluate the efficacy of Peposertib in terms of Pathological Clinical Response
(pCR)/Clinical Complete Response (cCR) when administered in combination with capecitabine and
RT versus placebo, capecitabine, and RT in Phase II.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase Ib: Peposertib + Capecitabine + RT | Experimental | | - Phase Ib: Peposertib
- Capecitabine
|
Phase II: Peposertib + capecitabine + RT | Experimental | | - Capecitabine
- Phase II: Peposertib
|
Phase II: Placebo + capecitabine + RT | Placebo Comparator | | - Capecitabine
- Phase II: Placebo
|
Eligibility Criteria
Inclusion Criteria:
- Participants who have an Eastern Cooperative Oncology Group Performance Status less
than or equals to (<=) 1
- Participants who have histologically confirmed and localized resectable rectal cancer
(Stage 3)
- Participants who received induction chemotherapy are allowed to be enrolled to this
study except this induction is resulting in clinical complete response (cCR) or tumor
progression
- Participants who have lower edge of the tumor located in rectum
- Adequate hematological, hepatic and renal function as defined in the protocol
- Male participants if they agree to the following during the study intervention period
and for at least 12 weeks after the last dose of study intervention
- Female participants are eligible if not pregnant or breastfeeding
- Other protocol defined inclusion criteria could apply
Exclusion Criteria:
- Participants with history of any other significant medical disease or psychiatric
conditions that might in the assessment of the Investigator preclude safe
participation in the study
- Participants with history of difficulty swallowing, malabsorption, or other chronic
gastrointestinal disease or conditions that may hamper compliance and/or absorption of
the study intervention
- Unstable cardiovascular function within 6 months prior to enrollment
- Hypertension uncontrolled by medication (ie, systolic blood pressure >= 150 millimeter
of mercury (mmHg) and diastolic blood pressure >= 90 mmHg)
- Participants with history of other malignant disease within the past 5 years, other
than successfully treated basal carcinoma of the skin or carcinoma in situ of the
cervix
- Participants with known human immunodeficiency virus positivity, known active
hepatitis (for example, hepatitis B virus or hepatitis C virus), current alcohol
abuse, or cirrhosis
- Participants with ongoing active infection or treatment with a live attenuated vaccine
within 4 weeks of dosing
- Participants with concomitant use of H2-blocker or proton pump inhibitors (PPIs) (or
unable to stop at least 5 days prior to the first treatment). Note that calcium
carbonate is acceptable
- Participation in any interventional clinical study within 28 days prior to Screening
or during participation in this study
- Other protocol defined exclusion criteria could apply.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase Ib: Number of Participants Experiencing a Dose Limiting Toxicity (DLT) |
Time Frame: | Time from first dose of study drug to end of chemo radiotherapy with a final assessment at 4 weeks post-surgery |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Phase Ib and II: Occurrence of Treatment-related Adverse Events (TEAEs) According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) version 5.0 |
Time Frame: | Time from first dose of study drug to final assessment at 5 years for each phase |
Safety Issue: | |
Description: | |
Measure: | Phase Ib and II: Number of Participants With Abnormalities (Grade Greater than or equals to (>=) 3) in Laboratory Test Values |
Time Frame: | Time from first study drug to final assessment at 5 years for each phase |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Number of Participants With Markedly Abnormal Vital Sign Measurements |
Time Frame: | Time from first dose of study drug to final assessment at 5 years for each phase |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings |
Time Frame: | Time from first dose of study drug to final assessment at 5 years for each phase |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Overall Survival |
Time Frame: | Time from first dose of study drug to final assessment at 5 years |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Disease-free Survival |
Time Frame: | Time from first study drug to final assessment at 5 years |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Best Overall Response Assessed by Investigator |
Time Frame: | Time from first dose of study drug until surgery at Day 119 |
Safety Issue: | |
Description: | |
Measure: | Phase Ib and II: Time from Surgery to Local Recurrence and Distant Metastasis |
Time Frame: | Time from surgery to final assessment at 5 years for each phase |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Maximum Observed Drug Concentration (Cmax) of Peposertib |
Time Frame: | Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day (FD1) and Fraction Day 9 |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (tlast) (AUC0-t) of Peposertib |
Time Frame: | Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Time to Reach Maximum Plasma Concentration (tmax) of Peposertib |
Time Frame: | Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Total Body Clearance of Drug From Plasma Following Oral Administration (CL/f) of Peposertib |
Time Frame: | Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 for each phase for each phase |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Apparent Volume of Distribution (Vz/f) of Peposertib |
Time Frame: | Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 for each phase |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Apparent Terminal Half-life (t1/2) of Peposertib |
Time Frame: | Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 |
Safety Issue: | |
Description: | |
Measure: | Phase II: Overall Survival |
Time Frame: | Time from randomization to final assessment at 5 years |
Safety Issue: | |
Description: | |
Measure: | Phase II: Best Overall Response Assessed by Investigator |
Time Frame: | Time from randomization until Day 119 |
Safety Issue: | |
Description: | |
Measure: | Phase II: Neoadjuvant Rectal Score |
Time Frame: | Post-surgery at Day 119 |
Safety Issue: | |
Description: | |
Measure: | Phase II: Proportion of Participants With/Without Surgical Intervention |
Time Frame: | Time from randomization to final assessment at 5 years |
Safety Issue: | |
Description: | |
Measure: | Phase II: Number of Participants With R0 Resection (No Residual Tumor) |
Time Frame: | Post-surgery at Day 119 |
Safety Issue: | |
Description: | |
Measure: | Phase II: Quality of Life (QoL) Measured Using European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) |
Time Frame: | Time from randomization to assessment at 2 years |
Safety Issue: | |
Description: | |
Measure: | Phase II: Quality of Life (QoL) Measured Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Colorectal Cancer (EORTC-CR29) |
Time Frame: | Time from randomization to assessment at 2 years |
Safety Issue: | |
Description: | |
Measure: | Phase II: Quality of Life (QoL) Measured Using EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) |
Time Frame: | Time from randomization to assessment at 2 years |
Safety Issue: | |
Description: | |
Measure: | Phase Ib and II: Proportion of Participants With Pathological Complete Response (pCR) |
Time Frame: | Post-surgery at Day 119 |
Safety Issue: | |
Description: | |
Measure: | Phase Ib: Proportion of Participants With Clinical Complete Response (cCR) |
Time Frame: | Time from first study drug until 1 to 2 weeks prior to surgery |
Safety Issue: | |
Description: | |
Measure: | Phase II: Proportion of Participants With Clinical Complete Response (cCR) |
Time Frame: | Time from randomization until surgery at Day 119 |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | EMD Serono Research & Development Institute, Inc. |
Trial Keywords
- DNA-PK inhibitor
- Peposertib
- capecitabine
Last Updated
June 24, 2021